The following results have been obtained during the past year: (1) Desensitization to the effects of Beta-receptor agonists occurs in tracheal smooth muscle isolated from rats pretreated with these agonists. (2) In vivo-induced desensitization results from changes in the affinity of Beta-receptors for agonist drugs, as was observed in the in vitro-induced desensitization. (3) In vivo-induced desensitization is limited to the Beta-receptor per se and apparently does not affect other sites such as the phosphodiesterase enzymes which control the intracellular levels of cyclic AMP. During the evaluation of Beta-receptor affinity changes in tracheas removed from in vivo pretreated rats, it was noted that terbutaline, a new specific Beta 2-receptor agonist, was less effective than the catecholamines as a spasmolytic and exhibited an interaction with the Beta-receptor antagonist drug, propranolol, which apparently was not competitive. Studies in the second year will be designed to answer the following questions: (1) Does terbutaline, a drug purported to be a highly specific Beta 2-receptor agonist, really interact at Beta 2-receptors? (2) Are alpha-receptors present in tracheal smooth muscle? and (3) Does desensitization or Beta-receptor blockade unmask the alpha-receptors?